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My most popular posts in 2015 (part II)
Techno-optimism
For several years now, I have grown more optimistic about the power of human innovation. Despite the barrage of bad news, the fact is that we are richer and healthier than we have ever been. Yes, I might not be rich or healthy compared to the luckiest among us… but on the whole, humanity has been doing well.
In Going beyond our limitations, I reflected on the “coming” end of Moore’s law. Our computers are using less power and they have chips that are ever smaller… but it is seemingly more and more difficult to improve matters. I argue that some of the pessimism is unwarranted: on the whole, we are still making nice progress… But it is true that, at the margin, we are facing challenges. I think we need to take them head on because I want robots in my blood hunting down diseases and chips in my brain helping me think more clearly. In Could big data and wearables help the fight against diseases?, I argue that information technology could massively accelerate medical research.
In What a technology geek sees when traveling abroad, I reflect on how technology has evolved, by using a recent trip I made as a vantage point. In Amazing technologies from the year 2015…, I reflect on the technological progress we made in 2015.
This year, I read Rainbows end, a famous novel by Vernor Vinge set in 2025. The novel makes some precise prediction about 2025, one of them is that we shall cure Alzheimer’s by then (at least for some individuals). Interestingly, Hilary Clinton has announced a plan to do just that, should she be elected president of the USA. In Revisiting Vernor Vinge’s “predictions†for 2025, I have looked at the novel as a set of predictions, trying to sort them out into what is possible and what is less likely.
Aging
I like to stress how blind I can be to the obvious. I have a lot of education, probably too much education… but I am routinely wrong in very important ways. For example, I took biology in college and I got excellent grades. I attended really good schools. I studied hard. I have also been a gardener for most of my life. I have also kept green plants in my home for decades. Yet, until I reached my forties, I assumed that plants took most of their mass from the soil they were planted in. How could I ever think that? It is obviously deeply wrong. (In case you are also confused, plants are mostly made out of the carbon their extract from the CO2 in the air.) I just kept on assuming, even though I had all the facts at my disposal, and presumably all the required neurons, to know better.
And up till 2015, I assumed that aging was both unavoidable and irreversible. I guess I assumed that evolution had tuned bodies for an optimal lifespan and that whatever we got was the best we could get. After all, you buy a car and it lasts more or less ten years. You buy a computer and it lasts more or less five years. It makes sense, intuitively, that all biological organisms would have an expiry date based on wear and tear.
Yet this makes no sense. For example, I keep annual plants in my basement, making them perennial by pruning their flowers just before they bloom. If evolution drove living things to live as long as possible, these annual plants would be perennial. Yet we know that evolution did the opposite. We believe that plants were originally perennial and then became annual more recently in their evolution. In Canada, we have the Pacific salmon that dies out horribly after procreation while the similar Atlantic salmon can reproduce many times. There is a worm, the Strongyloides ratti that can live 400 days in its asexual form while only 5 days in its sexual form. So the very same worm, with the same DNA, can “choose” to live a hundred of times longer, or not. Many animal species like whales, some fishes (sturgeon and rougheye rockfish), some turtles, lobster do not age like we do… and they sometimes even age in reverse… meaning that their risk of death decreases with time while their fertility might go up.
So, clearly, we age because the body does not do everything it should to keep us in good shape. There are some forms of damage that your body cannot repair, but it could do a whole lot more. There is some kind of clock ticking… it is either the case that your body “wants” you to age on a schedule (like annual plants), or else your genes are simply ill-suited for longevity (because evolution does not care about what happens to the old). Whatever the case might be, aging is mostly a genetic disease we all suffer from.
It is all nice but what does it matter to us, human beings? Ten years ago at Stanford, Irina Conboy and her collaborators showed that the blood of a young mouse could effectively “rejuvenate” an old mice. This was a significant breakthrough but it got little traction… until recently. How does it work? Conboy knew that when we do organ transplantation, it is the age of the recipient that matters. If you put a young lung into an old body, it behaves like an old lung. And vice versa: an old hearth in a young body will act young. We now know that tissues respond to signals: if told to be young, cells behave as if they were young. We have been able to take cells from centenarians and reset them so that they look like young cells. So can you tell your body that you are young again? Drinking young blood won’t work, of course… instead, we want to identify the signals and tweak them accordingly. Recently, the Conboy lab. at UC Berkeley showed that oxitocin (a freely available hormone) could rejuvenate old muscles. There are ongoing clinical trials focusing on myostatin inhibition to allow old people to have normal muscle mass and strength. The race is currently on to identify these signals and find ways to modulate them: old signals should be silenced and young signals should be amplified. There are many ways to silence or amplify a signal, but because we do not have the cipher book, it is tricky business.
Harvard geneticist George Church has other angles of attack and he claims that “in just five or six years he will be able to reverse the aging process in human beings.” Church has been studying the genes of centenarians and he wants to identify protective alleles that we could then all receive through genetic engineering. Moreover, he has plans to up-regulate (and possibly down-regulate) certain genes. Indeed, as we age, many genes that were silent, are activated, and a few that were active are down-regulated. This gene regulation is part of what we call “perigenetic”: though your genes might be set for life, which genes are expressed at any given time is a dynamic and reversible process. So cells know how to be old or young and this seems to depend a lot of which genes are expressed. The process is also fully reversible as far as we can tell. Will George Church cure aging by 2020?
As it turns out, there are many other rejuvenation therapies in the works. As you get older, your immune system starts to fail and even turn against you. Part of this process is that you effectively lose your thymus (around age 40): it becomes atrophied. The thymus is the organ in charge of “training” your immune cells. With it gone, your immune system gradually becomes incompetent. There are many ways to restore the thymus. There is an ongoing clinical trial to make controlled used of hormones to regrow it. Gene therapies could also work, as well as various transplantation approaches. Setting the thymus aside, it is more and more common that we create immune cells in a laboratory and inject them. This could be used to boost the immune system of the very old.
Stem cells therapies are fast growing. We are able, in principle, to take some of your skin cells, turn them into stem cells and then inject them back into your body so that they go on to act as new stem cells to help repair your joints or your brain. There is an endless stream of therapies in clinical trials right now. Not everything works as expected… one particular problem is that stem cells signal and respond to signalling… this means that how a given stem cell will behave in a given environment is complicated. Just randomly dumping stem cells in your body is likely ineffective… but scientists are getting more sophisticated.
Your body produces a lot of garbage as you grow old. The garbage accumulates. In particular, amyloids clog your brain and your heart and eventually kill you. Also some of your cells reach the end of their life but instead of just self-destroying (apoptosis), they just sit around and emit toxic signals. We already had clinical trials to clear some of this garbage… the results have not been overly positive. But what is more encouraging is that we have developed the technology… should we ever need it.
In any case, for me, 2015 was the year I realized that we are aging because we lack the technology to stay young. I have qualified aging as a software bug. We have the software of life, we can tweak it, and we think we can “upgrade” the software so that aging is no longer a feature. We don’t know how long this might take… could be centuries, could be decades… but I think we will get there as a species. In 2015, the first clinical trial for an “anti-aging” pill was approved (metformin). This pill would, at best, slow down a little bit aging… but the trial is important as a matter of principle: the American government has agreed that we could test an anti-aging therapy. I have written about how astronauts mysteriously age in space. As far as I can tell, this remains mostly unexplained. Radiations, gravity, aliens?
Scholarship
In Identifying influential citations, I reported on the launch of Semantic Scholar, an online tool to search for academic references that innovates by distinguishing meaningful citations from de rigueur ones. I also reacted to the proposal by some ill-advised researchers to ban LaTeX in favor of Microsoft Word for the production of research articles.
Math education
I think that math. education is still far from satisfying. In On rote memorization and antiquated skills and Other useless school trivia: the quadratic formula, I attempted to document how we spend a lot of effort teaching useless mathematical trivial to millions of kids, for no good reason that I can see. (I have a PhD in Mathematics and I have published research papers in Mathematics.)